NM_001243093.2:c.3+17649C>T

Variant names:

• chr5-39252920-G-A
• rs7700754
• NM_001243093.2:c.3+17649C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243093.2(FYB1):​c.3+17649C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,106 control chromosomes in the GnomAD database, including 9,552 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9552 hom., cov: 33)
• Consequence: FYB1 NM_001243093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 5 publications found

Genes affected

FYB1 (HGNC:4036): (FYN binding protein 1) The protein encoded by this gene is an adapter for the FYN protein and LCP2 signaling cascades in T-cells. The encoded protein is involved in platelet activation and controls the expression of interleukin-2. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

FYB1 Gene-Disease associations (from GenCC):

• thrombocytopenia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243093.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	NM_001243093.2		c.3+17649C>T		intron	N/A	NP_001230022.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000646045.2		c.3+17649C>T		intron	N/A	ENSP00000493623.1
	FYB1	ENST00000510188.1	TSL:3	c.-28+21483C>T		intron	N/A	ENSP00000426597.1
	FYB1	ENST00000512138.1	TSL:3	c.-163-2114C>T		intron	N/A	ENSP00000424919.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48891 AN: 151988 Hom.: 9535 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48944 AN: 152106 Hom.: 9552 Cov.: 33 AF XY: 0.320 AC XY: 23762 AN XY: 74350

African (AFR) AF: 0.555 AC: 23040 AN: 41480

American (AMR) AF: 0.303 AC: 4629 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5174

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4820

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14350 AN: 68000

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.248 Hom.: 6801

Bravo AF: 0.338

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.60
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7700754; hg19: chr5-39253022;